Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.

Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.

A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology.

BACKGROUND: Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles. METHODS: Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we compared and characterized the EV fraction isolated with this novel method with a classical digestion-based EV isolation procedure. Moreover, EV biogenesis was pharmacologically manipulated with either GW4869 or picrotoxin to assess the validity of the spontaneous-release method, while the injection of labelled-EVs into the mouse brain further supported the integrity of the isolated vesicles. RESULTS: We hereby present an efficient purification method that captures a sEV-enriched population spontaneously released by mouse and human brain tissue. In addition, we tested the significance of the release method under conditions where biogenesis/secretion of sEVs was pharmacologically manipulated, as well as under animals' exposure to chronic stress, a clinically relevant precipitant of brain pathologies, such as depression and Alzheimer's disease. Our findings show that the released method monitors the drug-evoked inhibition or enhancement of sEVs secretion while chronic stress induces the secretion of brain exosomes accompanied by memory loss and mood deficits suggesting a potential role of sEVs in the brain response to stress and related stress-driven brain pathology. CONCLUSIONS: Overall, the spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology. Video Abstract.

Acute bouts of aerobic and resistance exercise similarly alter inhibitory control and response time while inversely modifying plasma BDNF concentrations in middle-aged and older adults with type 2 diabetes.

Impairments in several domains of cognitive functions are observed in people with Type 2 Diabetes Mellitus (T2DM), often accompanied by low Brain-derived neurotrophic factor (BDNF) concentrations. Although aerobic and resistance exercise enhances cognitive functions and raises BDNF concentrations in several populations, it remained uncertain in T2DM subjects. This study compared the effects of a single bout of aerobic (AER, 40 min of treadmill walk at 90-95% of the maximum walk speed) or resistance (RES, 3 × 10 repetitions in eight exercises at 70% of 10-RM) exercise on specific cognitive domain performance and plasma BDNF concentrations of physically active T2DM subjects. Eleven T2DM subjects (9 women/2 men; 63 ± 7 years) performed two counterbalanced trials on non-consecutive days. Stroop Color and Word (SCW) task [assessing the attention (congruent condition) and inhibitory control (incongruent condition)], Visual response time (assessing the response time), and blood collection (for plasma BDNF concentrations) were performed pre and post-exercise sessions. With distinct magnitude, both AER and RES improved the incongruent-SCW (d = - 0.26 vs. - 0.43 in AER and RES, respectively; p < 0.05), RT(best) (d = - 0.31 vs. - 0.52, p < 0.05), and RT(1-5) (d = - 0.64 vs. - 0.21, p < 0.05). The congruent-SCW and RT(6-10) were not statistically different. Plasma BDNF concentrations were elevated 11% in AER (d = 0.30) but decreased by 15% in RES (d = - 0.43). A single session of aerobic or resistance exercise similarly improved the inhibitory control and response time of physically active T2DM subjects. Nevertheless, aerobic and resistance exercise sessions induced an opposite clinical effect in plasma BDNF concentrations.

Microcephaly as a risk factor for dental alterations: A case-control study.

OBJECTIVE: This study aimed to assess whether microcephaly is a risk factor for alterations in the chronology and sequence of tooth eruption and for developmental defects of enamel. MATHERIALS AND METHODS: In this case-control study, 81 children aged 30-36 months, including 40 normoreactive children and 41 with microcephaly, were submitted to oral clinical examination to determine the frequency of alterations in the chronology and sequence of tooth eruption and developmental enamel defects. The sample was matched for sex and age (1:1) and allocated to the case (presence of dental alterations) and control (absence of dental alterations) groups. Gestational age, birthweight and socioeconomic characteristics were also analyzed. Chi-square test and Fisher's exact test were applied (α = 0.05). RESULTS: Microcephaly was significantly associated with delayed tooth eruption, alterations in the sequence of tooth eruption, and defects in dental enamel (p < 0.001). Low birthweight also showed a significant association with this alterations (p < 0.005) and prematurity was associated with defects in enamel development (p < 0.005). CONCLUSION: Microcephaly is a risk factor for alterations in the tooth eruption process and enamel formation in primary teeth.

Cobalt Ferrite Synthesized Using a Biogenic Sol-Gel Method for Biomedical Applications.

Cancer is one of the leading causes of death worldwide. Conventional treatments such as surgery, chemotherapy, and radiotherapy have limitations and severe side effects. Magnetic hyperthermia (MH) is an alternative method that can be used alone or in conjunction with chemotherapy or radiotherapy to treat cancer. Cobalt ferrite particles were synthesized using an innovative biogenic sol-gel method with powder of coconut water (PCW). The obtained powders were subjected to heat treatments between 500 °C and 1100 °C. Subsequently, they were characterized by thermal, structural, magnetic, and cytotoxic analyses to assess their suitability for MH applications. Through X-ray diffraction and Raman spectroscopy, it was possible to confirm the presence of the pure phase of CoFe2O4 in the sample treated at 1100 °C, exhibiting a saturation magnetization of 84 emu/g at 300 K and an average grain size of 542 nm. Furthermore, the sample treated at 1100 °C showed a specific absorption rate (SAR) of 3.91 W/g, and at concentrations equal to or below 5 mg/mL, is non-cytotoxic, being the most suitable for biomedical applications.

Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocampal malfunction.

Emerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer's disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD and have been shown to trigger intracellular Tau accumulation and downstream Tau-dependent neuronal dysfunction. However, the mechanisms through which stress and GC disrupt Tau clearance and degradation in neurons remain unclear. Here, we demonstrate that Tau undergoes degradation via endolysosomal sorting in a pathway requiring the small GTPase Rab35 and the endosomal sorting complex required for transport (ESCRT) machinery. Furthermore, we find that GC impair Tau degradation by decreasing Rab35 levels, and that AAV-mediated expression of Rab35 in the hippocampus rescues GC-induced Tau accumulation and related neurostructural deficits. These studies indicate that the Rab35/ESCRT pathway is essential for Tau clearance and part of the mechanism through which GC precipitate brain pathology.

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes.

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice.

Rare earth elements - Source and evolution in an aquatic system dominated by mine-Influenced waters.

Acid mine drainage (AMD), formed by the instability of sulfides, typically generates acidity and releases potentially toxic elements and sulfate to the environment, among other pollutants. An example is the group of rare earth elements (REE) that may have high toxic behavior. This toxicity leads to degradation of soils, water reservoirs and rivers, promoting serious risks for the ecosystems. So, the main goal of the present work is to study the hydrochemical properties of a system with mine-influenced waters during the rainy season, focusing on the origin, evolution/behavior, and concentration of REE. The study area is the São Domingos mining complex, located in one of the largest metallogenetic provinces in the world (Iberian Pyrite Belt), known by the evidences of AMD contamination. The obtained results reveal extraordinarily low pH (0.4), high electrical conductivity, reaching 26,200 µS/cm, and high values of sulfate and acidity. Regarding the REE, the determined concentration exceeded that observed in normal pH of neutral freshwaters by 2-3 times the order of magnitude. The results revealed that Y and Ce are distinguished in practically all sampled sites, due to its higher concentrations, with maximum values of 221.8 and 166.9 µg/L. In general, the concentrations increase as the water pH decreases. The statistical analysis indicates that REE elements may have a common origin, mutual dependence, and similar behavior during transport with typical AMD elements and composition of host rocks. Most samples show enrichment in middle REE (MREE) (Gdn/Lun), like the classic signature of AMD. In turn, colloids and AMD-precipitates may be participating in the incorporation of these elements. Therefore, due to potential risk of impacts on ecosystems, REE are a topic of relevant interest for future studies in order to assist monitoring processes and help government decisions related to water quality management.

Melatonin regulates maternal pancreatic remodeling and B-cell function during pregnancy and lactation.

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well-known the role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents. The present study investigated the role of melatonin on energy metabolism and in pancreatic function and remodeling during pregnancy and early lactation in rats. The results confirm that the absence of melatonin during pregnancy impairs glucose metabolism. In addition, there is a dysregulation in insulin secretion at various stages of the development of pregnancy and an apparent failure in the glucose-stimulated insulin secretion during the lactation period, evidencing the role of melatonin on the regulation of insulin secretion. This mechanism seems not to be dependent on the antioxidant effect of melatonin and probably dependent on MT2 receptors. We also observed changes in the mechanisms of death and cell proliferation at the end of pregnancy and beginning of lactation, crucial periods for pancreatic remodeling. The present observations strongly suggest that both functionality and remodeling of the endocrine pancreas are impaired in the absence of melatonin and its adequate replacement, mimicking the physiological increase seen during pregnancy, is able to reverse some of the damage observed. Thus, we conclude that pineal melatonin is important to metabolic adaptation to pregnancy and both the functionality of the beta cells and the remodeling of the pancreas during pregnancy and early lactation, ensuring the return to nonpregnancy conditions.

Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming.

Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism's physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.

Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine.

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder's cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.

Prevalence of malocclusions in children with microcephaly associated with the Zika virus.

INTRODUCTION: The objectives of this study were to determine the prevalence of malocclusion among children with Zika virus-associated microcephaly (MZV) and to describe the most common malocclusion in this population. METHODS: This was a cross-sectional study including patients aged between 30 and 36 months diagnosed with MZV. Healthy children were randomly selected with the same sociodemographic characteristics as the control group. Information about arch-type, primate spaces, arch form, overbite, overjet, midline deviation, anterior crossbite, anterior open bite, and the posterior crossbite was recorded. The statistical analysis used descriptive analysis, Pearson chi-square test, and multivariate logistic regression. RESULTS: Forty children comprised the MZV group, and 40 comprised the control group. Our results demonstrated a significantly higher prevalence of malocclusions in children who had MZV than the control group (P <0.001). Patients with MZV were more likely to have late eruption (P <0.001), hypoplastic maxillary arch (P <0.001), hypoplastic mandibular arch (P <0.001), excessive overjet (P <0.001), and posterior crossbite (P = 0.004). CONCLUSIONS: The prevalence of malocclusion was higher among children with MZV. Late eruption, hypoplastic maxillary arch, hypoplastic mandibular arch, excessive overjet, and posterior crossbite were the most common characteristics for this population.

Stress and the Etiopathogenesis of Alzheimer's Disease and Depression.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology whose initiators are poorly defined. Accumulating clinical and experimental evidence suggests a causal role of lifetime stress in AD. This chapter summarizes current knowledge about how chronic stress and its accompanying high levels of glucocorticoid (GC) secretion, trigger the two main pathomechanisms of AD: (i) misprocessing of amyloid precursor protein (APP) and the generation of amyloid beta (Aß) and (ii) Tau hyperphosphorylation and aggregation. Given that depression is a well-known stress-related illness, and the evidence that depression may precede AD, this chapter also explores neurobiological mechanisms that may be common to depressive and AD pathologies. This review also discusses emerging insights into the role of Tau and its malfunction in disrupting neuronal cascades and neuroplasticity and, thus triggering brain pathology.

Lipid-core nanocapsules are an alternative to the pulmonary delivery and to increase the stability of statins.

Aims: Lipid-core nanocapsules (LNCs) loaded with simvastatin (SV, SV-LNC) or lovastatin (LV, LV-LNC) were formulated for pulmonary administration. Methods: The LNC suspensions were characterized physicochemically, their stability was evaluated, and drug delivery by the pulmonary route was tested in vitro. Results: The loaded LNCs had a particle size close to 200 nm, a low polydispersity index, and a zeta potential around -20 mV. The encapsulation efficiency was high for SV (99.21 ± 0.7%) but low for LV (20.34 ± 1.2%). SV release from nanocapsules was slower than it was from SV in solution, with a monoexponential release profile, and the drug emitted and aerosol output rate was higher for SV-LNCs (1.58 µg/s) than for SV in suspension (0.54 µg/s). Conclusions: SV-LNCs had a median aerodynamic diameter of 3.51 µm and a highly respirable fraction (61.9%), indicating that nanoparticles are a suitable system for efficient delivery of simvastatin to the lung.

Monitoring Translation Activity of mRNA-Loaded Nanoparticles in Mice.

Targeting mRNA to eukaryotic cells is an emerging technology for basic research and provides broad applications in cancer immunotherapy, vaccine development, protein replacement, and in vivo genome editing. Although a plethora of nanoparticles for efficient mRNA delivery exists, in vivo mRNA targeting to specific organs, tissue compartments, and cells remains a major challenge. For this reason, methods for reporting the in vivo targeting specificity of different mRNA nanoparticle formats will be crucial. Here, we describe a straightforward method for monitoring the in vivo targeting efficiency of mRNA-loaded nanoparticles in mice. To achieve accurate mRNA delivery readouts, we loaded lipoplex nanoparticles with Cre-recombinase-encoding mRNA and injected these into commonly used Cre reporter mouse strains. Our results show that this approach provides readouts that accurately report the targeting efficacy of mRNA into organs, tissue structures, and single cells as a function of the used mRNA delivery system. The method described here establishes a versatile basis for determining in vivo mRNA targeting profiles and can be systematically applied for testing and improving mRNA packaging formats.

Combined Effects of Dissolved Nutrients and Oxygen on Plant Litter Decomposition and Associated Fungal Communities.

Aquatic ecosystems worldwide have been substantially altered by human activities, which often induce changes in multiple factors that can interact to produce complex effects. Here, we evaluated the combined effects of dissolved nutrients (nitrogen [N] and phosphorus [P]; three levels: concentration found in oligotrophic streams in the Cerrado biome, 10× and 100× enriched) and oxygen (O2; three levels: hypoxic [4% O2], depleted [55% O2], and saturated [96% O2]) on plant litter decomposition and associated fungal decomposers in laboratory microcosms simulating stream conditions under distinct scenarios of water quality deterioration. Senescent leaves of Maprounea guianensis were incubated for 10 days in an oligotrophic Cerrado stream to allow microbial colonization and subsequently incubated in microcosms for 21 days. Leaves lost 1.1-3.0% of their initial mass after 21 days, and this was not affected either by nutrients or oxygen levels. When considering simultaneous changes in nutrients and oxygen concentrations, simulating increased human pressure, fungal biomass accumulation, and sporulation rates were generally inhibited. Aquatic hyphomycete community structure was also affected by changes in nutrients and oxygen availability, with stronger effects found in hypoxic treatments than in depleted or saturated oxygen treatments. This study showed that the effects of simultaneous changes in the availability of dissolved nutrients and oxygen in aquatic environments can influence the activity and composition of fungal communities, although these effects were not translated into changes in litter decomposition rates.

Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans.

Pelargonium graveolens is a member of the Geraniaceae family and has been used in folk medicine in many countries because of its anti-inflammatory activity. No studies have yet been reported to evaluate the anti-inflammatory activity of a nanoemulsion containing geranium oil (GO) model in macrophages. In this study the anti-inflammatory effect of Geranium nanoemulsion (NEG) macrophages induced with soluble proteins of Candida albicans was investigated. GO presented citronellol (17.74%) and geraniol (14.43%) as main constituents. The characterization in NEG was demonstrated, showing the particle size of 164 ± 3.5 nm, PDI of 0.12 ± 0.006 and zeta potential -10 mV ± 1.7. The MIC obtained for NEG and GO were 3.64 µg ml-1 and 1.82 µg ml-1, respectively. The viability of the macrophages treated with NEG and GO concentrations (1/2 x, 1x and 2x MIC) was evaluated. There was a significant reduction of viability and the MTT assay was not confirmed after the LDH assay. Anti-inflammatory activity was evaluated by determining nitric oxide (NO), cytokines (interleukin IL-1, IL-6 and IL-10), tumor necrosis factor-α (TNF) and the expression levels gene of interleukin (IL-2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The apoptosis inhibition capacity was assessed by determination of INFγ, caspase 3 and caspase 8. The results indicated that there was a significant increase of NO in the levels after treatment with NEG and significantly reduced levels after treatment with GO. The cytokines (IL-1, IL-6, IL-10, and TNF) were evaluated and NEG (½ x, 1x MIC) decreased IL-1 levels by 1.25-1.37 times, respectively. The NEG did not decrease IL-6 levels and a significant increase was observed for IL-10. GO significantly decreased IL-6 and IL-10 levels. There was a significant decrease in IL-2 and COX-2 levels and increased levels of iNOs. The levels of IFNγ and caspase-3 after treatment with NEG decreased indicating an anti-inflammatory effect and can inhibit apoptosis. Finally, the levels of caspase-8 do not change. Thus, pretreatment with NEG induced an anti-inflammatory effect against soluble proteins of C. albicans model macrophages.

Anti-Candida activity assessment of Pelargonium graveolens oil free and nanoemulsion in biofilm formation in hospital medical supplies.

Infections due to microbial biofilm formation on the surface of catheters and other medical devices are constantly reported as a major cause of morbidity and mortality in patients admitted to hospitals. Furthermore, sessile cells are more resistant to phagocytosis and most antimicrobial, which complicates the treatment of such infections. Researches aimed at new antimicrobial originating mainly from plants have increased in recent years and the development of new strategies for their release is critical in combating the formation of biofilms. Geranium oil (GO) has proven antimicrobial activity. Because of this, the aim of this study was to develop nanoemulsions containing this oil (NEG) and evaluate its activity after the biofilm formation of Candida albicans, Candida tropicalis, Candida glabrata, and Candida krusei in hospital medical supplies. For quantification of the biofilm, crystal violet, total protein, and ATP-bioluminescence assays were used. The results revealed that GO and NEG showed lower MIC for C. albicans and C. tropicalis. The biofilms formed by different species of Candida on the surfaces of polyethylene and polyurethane were quantified. GO and NEG significantly inhibited the formation of biofilms in all species tested on the surfaces of polyethylene. However, NEG antibiofilm has had better activity than GO for C. albicans, C. tropicalis and C. glabrata, according to the surface potential analysis by atomic force microscopy (AFM). The analysis of the biofilm formation on the polyethylene surface by ATP-bioluminescence and CFU showed similar results. In both methods the formation of biofilm in the catheter occurred in greater quantity for C. albicans and C. tropicalis. GO did not significantly inhibit the formation of biofilms only in C. krusei, although NEG significantly increased this activity GO in all species tested when compared to the control training biofilm. The following study shows that the development of NEG may become an effective alternative to reduce the adhesion of microorganisms and prevent infections resulting from the use of some hospital medical materials.

Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.

Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GC levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis. Dexamethasone (DEX) was administered noninvasively to the mothers via drinking water between the 14th and the 19th days of pregnancy. Mothers were subjected to glucose and insulin tolerance tests at 1, 2, 3, 6, and 12 mo postweaning. Pregnant rats not treated with DEX and age-matched virgin rats were used as controls. Pancreatic islets were isolated at the 20th day of pregnancy and 12 mo postweaning in order to evaluate glucose-stimulated insulin secretion. The expression of the miR-29 family was also studied due to its responsiveness to GCs and its well-documented role in the regulation of pancreatic ß-cell function. Rats treated with DEX during pregnancy presented long-term glucose intolerance and impaired insulin secretion. These changes correlated with 1) increased expression of miR-29 and its regulator p53, 2) reduced expression of syntaxin-1a, a direct target of miR-29, and 3) altered expression of genes related to cellular senescence. Our data demonstrate that the use of DEX during pregnancy results in deleterious outcomes to the maternal metabolism, hallmarked by reduced insulin secretion and glucose intolerance. This maternal metabolic programming might be a consequence of time-sustained upregulation of miR-29s in maternal pancreatic islets.